Effects of platelet-derived growth factor-AA on the healing process of tympanic membrane perforation

Abstract

Platelet-derived growth factor basic 30-kD disulfide-bonded dimer of A and B chains (PDGF-AA, PDGF AB, PDGF-BB) and a cytokine, promoting wound healing by its mitogenicity for fibroblast and by stimulating the production of fibronectin and hyaluronic acid. This article investigates the effect of PDGF on the healing process of tympanic membrane (TM) perforation. The pars tensa of the posterior aspect of the TM of rats was excised and treated with 2 microg of PDGF-AA or placebo. The animals were killed at 3, 5, 7, 9, 11, 15, and 28 days after operation. The healing process of TM perforation was observed with a telescope and light microscope. The temporal bones were also immunohistochemically examined for PDGF-alpha receptor (PDGF-R(alpha)) and fibronectin. All PDGF-AA-treated TM were completely closed by 5 days after surgery, whereas some of the placebo-treated TM were not closed at 15 postoperative days. PDGF-AA induced the most prominent proliferation of the connective tissue by 9 postoperative days, after which the growth of the connective tissue decreased. By the 4th postoperative week, the PDGF-treated TM were slightly thicker than normal TM. An intense expression of fibronectin was detected in the connective tissue layer of the TM that were treated with PDGF-AA. PDGF-R(alpha) was expressed in the epithelial layer of both the PDGF-treated and control TM. These results show that PDGF-AA speeds up the healing process of TM defect, improves the rate of healing, and prevents atrophic changes in the healed TM by promoting the connective tissue growth. The use of PDGF-AA can be an effective alternative to surgery for managing TM perforations.